Hydroxyproline Influence on Oxalate Metabolism

NCT02038543 | Completed Phase 1 Results DMC

• 2 other identifiers: 13-000150U54DK083908
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Primary hyperoxaluria is an inborn error of metabolism that results in marked overproduction of oxalate by the liver. The excess oxalate causes kidney failure and can cause severe systemic disease due to oxalate deposition in multiple body tissues. Metabolic pathways that lead to oxalate are poorly understood, but recent evidence suggests that hydroxyproline may play a role. Sources of hydroxyproline include the diet and bone turnover. If hydroxyproline can be confirmed as a significant factor in primary hyperoxaluria, diet modification might be of value in reducing the severity of disease. This protocol, in which hydroxyproline labelled with a cold isotope is infused intravenously in patients with primary hyperoxaluria, will allow the researchers to measure the amount of oxalate produced from hydroxyproline. The contribution of hydroxyproline metabolism to the amount of oxalate excreted in urine in will be able to be determined for patients with each of the known types of primary hyperoxaluria.

Conditions

Hyperoxaluria

Keywords

Hyperoxaluria; Oxalate; Primary Hyperoxaluria

Outcome Measures

Primary Outcomes (1)

• Mean Percent Conversion of Hydroxyproline (Hyp) to Urinary Oxalate (UOx)

  The overall contribution of hydroxyproline catabolism to urinary oxalate (UOx) and glycolate (UGlc) excretion is determined by the excess mole percent enrichment of urine with 13C2-oxalate and glycolate corrected for the fraction of labelled \[15N,13C5\]-Hyp that is circulating in the plasma.

  Participants will be followed for the duration of study infusion and observation, an average of 24 hours.

Secondary Outcomes (1)

• Mean Percent Conversion of Hydroxyproline (Hyp) to Urinary Glycolate (UGIc)

  Participants will be followed for the duration of the study infusion and observations, an average of 24 hours

Study Arms (1)

Primary hyperoxaluria patients

EXPERIMENTAL

Subjects will be infused with 13C5-hydroxyproline and 2H3-leucine for 6 hrs in the Clinical Research and Trials Unit (CRTU). The metabolic flux of 2H3-leucine has been well characterized, and is used as a control when studying the metabolism of trace infusions of labeled amino acids 3. Blood samples will be obtained every 30 min to determine the enrichment of plasma with 13C5-hydroxyproline and 2H3-leucine. Urine collections will be obtained hourly. The fluxes of whole body hydroxyproline and leucine will be calculated

Drug: Hydroxyproline and Leucine

Interventions

Hydroxyproline and Leucine DRUG

Subjects will be infused with 13C5-hydroxyproline and 2H3-leucine for 6 hrs in the CRTU. The metabolic flux of 2H3-leucine has been well characterized, and is used as a control when studying the metabolism of trace infusions of labeled amino acids 3. Blood samples will be obtained every 30 min to determine the enrichment of plasma with 13C5-hydroxyproline and 2H3-leucine. Urine collections will be obtained hourly. The fluxes of whole body hydroxyproline and leucine will be calculated

Also known as: 13C5-hydroxyproline, 2H3-leucine

Primary hyperoxaluria patients

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of primary hyperoxaluria (PH)
• Estimated Glomerular Filtration Rate (eGFR) (by serum creatinine) \> 50ml/min/1.73m\^2 - Patients with a diagnosis of PH I, PH II, PH III, or Non I/Non II/Non III PH (PH types will be confirmed by DNA)

You may not qualify if:

• eGFR \< 50 ml/min/1.73m\^2
• History of liver or kidney transplant
• Primary hyperoxaluria patients who have responded to pyridoxine therapy with reduction of urine oxalate excretion to \< 0.45 mmol/1.73m\^2/day
• Pregnancy

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institutes of Health (NIH): collaborator
• Rare Diseases Clinical Research Network: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic Hyperoxaluria Center

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Hyperoxaluria; Hyperoxaluria, Primary

Interventions

Hydroxyproline; Leucine

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proline; Imino Acids; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Branched-Chain; Amino Acids, Essential

Results Point of Contact

• Title: Dr. John C. Lieske
• Organization: Mayo Clinic

Lieske.John@mayo.edu

507-284-2064

Study Officials

• John C Lieske, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 19, 2013
• First Posted: January 16, 2014
• Study Start: September 1, 2013
• Primary Completion: September 1, 2016
• Study Completion: January 1, 2017
• Last Updated: July 2, 2017
• Results First Posted: July 2, 2017

Record last verified: 2017-06

Locations

US (1)